Helicobacter pylori has been recognized as the cause of gastric ulcers in humans. Rhesus monkeys are ubiquitously infected with H. pylori. Screening of sera from rhesus monkeys identified those lacking IgG antibody to H. pylori or H. pylori urease. Gastroscopy and biopsy collection of stomach mucosa showed the monkeys to be free of H. pylori organisms. Oral challenge of these monkeys with cultured H. pylori isolated from an Indian rhesus resulted in infection which was confirmed by culture and histology of the gastric mucosa. Colonization persisted for five months of observation. Rhesus monkeys naturally infected with H. pylori can be cleared of infection by 10 days of quadruple antibiotic therapy. Oral immunization of these monkeys with H. pylori urease plus the mucosal adjuvant, LT (Escherichia coli heat-labile endotoxin) resulted in development of antibody to the H. pylori urease. Challenge of vaccinated and unvaccinated H. pylori-free monkeys with cultured H. pylori resulted in lower colonization of the bacteria in the monkeys receiving the H. pylori urease vaccine revealed in biopsies taken by gastroscopy.